She departed New York on 16 October 1852 for Vera Cruz with the new Minister to Mexico, Judge Alfred Conkling, on board and returned to Norfolk on 27 November via Havana and Pensacola.

Her arrival in Chinese waters coincided with an important phase of Commodore Matthew C. Perry's expedition to open commercial relations with the Japanese.

On 14 February 1854 she entered Edo Bay with the rest of the squadron, remaining until the Convention of Kanagawa was signed on 31 March 1854 as part of Perry's show of force.

[1] The American government also at the same time chartered the steamer Hong Kong accompany Ward into the north and to return the remains of Ye Mingchen's for interment in Canton, 13 May 1859.

The Japanese embassy was formally composed of three men: Ambassador Shinmi Masaoki (新見正興), Vice-Ambassador Muragaki Norimasa (村垣範正), and Observer Oguri Tadamasa (小栗忠順).

Powhatan operated off Charleston, South Carolina from October 1862 to August 1863, captured schooner Major E. Willis on 19 April and sloop C. Routereau on 16 May, and deployed for a second time to the West Indies from November 1863 to September 1864 as flagship of Rear Admiral James L. Lardner.

[6] In 1877, the ship was ordered to Baltimore, Maryland along with the Swatara, on a peacekeeping mission following the city's riots, which occurred as part of the Great Railroad Strike of 1877.

[8] The ship ended her long and conspicuous career by making numerous cruises in Cuban waters to protect American commerce: July–August 1880, February–May 1882, January–May 1883, January–May 1885, and January–February 1886.